Ubiquitin specific protease 7 deubiquitinates and regulates Aurora B-mediated cytokinesis

Abstract

Aurora B is a widely studied mitotic checkpoint kinase that forms a part of the chromosomal passenger complex. The entry to and exit from mitosis are exquisitely controlled by Aurora B proteins, which regulate mitotic phases including chromosomal condensation, segregation, and cytokinesis, ensuring faithful propagation of daughter cells. Abnormal regulation of Aurora B proteins during the cell cycle can cause increased chromosomal segregation errors and ultimately lead to cancer. Thus, it is important to understand the key mechanisms that can modulate Aurora B protein levels during the cell cycle. Therefore, in this study we demonstrated the role of Ubiquitin-specific protease 7 (USP7) in regulating Aurora B protein level. Aurora B protein levels are upregulated when USP7 is dose-dependently increased, and downregulated when USP7 is depleted. By co-immunoprecipitation and Duolink assays, we demonstrated that USP7 interact with Aurora B. Furthermore, by treating cycloheximide we showed that USP7 extends the Aurora B protein half-life by its deubiquitinating activity. Finally, CRISPR/Cas9-mediated USP7 knockout produces severe nuclear structural defects causing multi-nucleation and cytokinesis failures, suggesting that the important role of USP7 during mitotic progression in stabilizing Aurora B.